title: Preclinical Alzheimer disease and risk of falls.
abstract: OBJECTIVE
  We determined the rate of falls among cognitively normal, community-dwelling older adults, some of whom had presumptive preclinical Alzheimer disease (AD) as detected by in vivo imaging of fibrillar amyloid plaques using Pittsburgh compound B (PiB) and PET and/or by assays of CSF to identify Aβ₄₂, tau, and phosphorylated tau.
  
  
  METHODS
  We conducted a 12-month prospective cohort study to examine the cumulative incidence of falls. Participants were evaluated clinically and underwent PiB PET imaging and lumbar puncture. Falls were reported monthly using an individualized calendar journal returned by mail. A Cox proportional hazards model was used to test whether time to first fall was associated with each biomarker and the ratio of CSF tau/Aβ₄₂ and CSF phosphorylated tau/Aβ₄₂, after adjustment for common fall risk factors.
  
  
  RESULTS
  The sample (n = 125) was predominately female (62.4%) and white (96%) with a mean age of 74.4 years. When controlled for ability to perform activities of daily living, higher levels of PiB retention (hazard ratio = 2.95 [95% confidence interval 1.01-6.45], p = 0.05) and of CSF biomarker ratios (p < 0.001) were associated with a faster time to first fall.
  
  
  CONCLUSIONS
  Presumptive preclinical AD is a risk factor for falls in older adults. This study suggests that subtle noncognitive changes that predispose older adults to falls are associated with AD and may precede detectable cognitive changes.
authors.affiliation: Program in Occupational Therapy, Washington University, St. Louis, MO, USA. starks@wusm.wustl.edu
authors.forename: Susan L
authors.initials: SL
authors.lastname: Stark
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Roe
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Grant
authors.forename: Holly
authors.initials: H
authors.lastname: Hollingsworth
authors.forename: Tammie L
authors.initials: TL
authors.lastname: Benzinger
authors.forename: Anne M
authors.initials: AM
authors.lastname: Fagan
authors.forename: Virginia D
authors.initials: VD
authors.lastname: Buckles
authors.forename: John C
authors.initials: JC
authors.lastname: Morris
mesh_terms: D000058:Accidental Falls; D000203:Activities of Daily Living / Q000523:psychology*; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000378:metabolism / Q000523:psychology*; D000814:Aniline Compounds / Q000378:metabolism; D015331:Cohort Studies; D042241:Early Diagnosis; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D011446:Prospective Studies; D012307:Risk Factors; D013844:Thiazoles / Q000378:metabolism
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D000814:Aniline Compounds; D013844:Thiazoles